The inflammatory response is a central means by which the immune system localizes and destroys antigens. Ineffective or inappropriate inflammatory reactions can, however, cause severe host tissue destruction such as that seen in conditions such as periodontal disease, rheumatoid arthritis, and systemic lupus erythematosus, to name but a few. This research will elucidate the mechanisms by which the immune system initiates and modulates inflammatory processes. In particular, we will determine the biochemical parameters involved in the chemotaxis of leukocytes including polymorphonuclear leukocytes, macrophages and lymphocytes. We recently developed methods for the study of chemotactic factor receptors on leukocytes using direct binding techniques. We will now attempt to isolate and characterize the oligopeptide chemotactic factor receptor on human granulocytes. We will also determine if human diseases such as periodontosis, periodontal disease or other inflammatory diseases are associated with abnormal numbers or functions of the chemotactic factor receptor. We have recently found that S-adenosyl methionine mediated methylation is required for the chemotactic responses of human monocytes. The type of methylation that is needed for chemotaxis and the nature of the methyl acceptor will be determined. In other studies, we found that normal mice develop leukopenia following an intraperitoneal injections of endotoxin, whereas, "non-responder" C3H/Hej mice do not. The development of leukopenia was found to be dependent upon the polysaccharide component of the endotoxin molecule. We are not attempting to determine which factors govern whether endotoxin does or does not produce neutropenia in mice. In sum, these studies will elucidate biochemical mechanisms of inflammation and attempt to characterize the factors which regulate the effectiveness and intensity of inflammaoory reactions.